1. Paediatric Tuberculosis in HIV Era
Diagnosis, Challenges and Management
Dr Mir Anwar
MBBS,DCH,MPH(USA)
Richmond Hospital,KZN, South Africa

2. 3rd SA TB Conference Durban 2012
This is a International and National TB/HIV conference attended by 1700 delegate from Home and abroad. I have the opportunity to attend the conference to update my knowledge in TB and HIV.12th June to 15th June 2012.

3. Overview Diagnosis of TB in HIV +ve Children Challenges
Management of Disease
New Developments
Here is an overview of what I will be covering in this talk. As the title suggests, I’ll cover 3 main issues
-Diagnosis of TB in HIV positive children
-Challenges that we face each and everyday as health care providers for these suffering children
-How we manage these condition
-And lastly I’ll be covering on some new and latest developments in the field.

4. HIV And TB Statistics 2010 data Opportunistic infection
8.8 million new TB cases Globally.
1.1 million Death (excluding HIV).
~1.1 million new HIV associated TB cases
82% living in Sub Saharan-Africa
350, 000 death
Opportunistic infection
20-37 times greater when HIV +ive
TB is the most common opportunistic infection in HIV positive patients, specially children. Why “Opportunistic"? Because this infection which may be caused by various strains of mycobacterium takes advantage of an immune system already weakened by HIV. In fact the risk of developing TB is times greater in people living with HIV as compared to those without HIV.
The combination of the two is fatal. TB is the leading cause of mortality among those living with HIV.
According to WHO statistics in 2010
There were an estimated 1.1 million new HIV/TB cases worldwide of which 82% were in Africa.
There was an estimated 350,000 deaths from these cases

5. Facts and Figures Deaths Worldwide South Africa HIV: 6000/day
TB: 5000/day
South Africa
TB cases : 4th in the world
Children: 16% of all TB cases
HIV/TB children : 25-60%
Let me begin with some facts and figure so you can visualize the severity of the conditions.
According to WHO
-HIV kills about 6000 people worldwide everyday and TB about 5000 people everyday, although TB is curable.
South Africa ranks 4 in the world in the number of TB cases with children accounting for 16% of all TB cases. Of these 16%, 25-60% are HIV +ve
Depending on the region of the country. Here in KwaZulu Natal Province where the HIV prevalence is quite high, I’m assuming the dual HIV/TB infected children is on the upper side...though I don’t have specific numbers.
There are various research going on in order to identify, prevent and treat infants, children and pregnant women with these dual diseases.
I’ve referenced these stats. For those of you who are interested, please contact me at the end of the presentation.

6. Diagnosis Recognizing symptoms Contact history Sputum culture
Chest X-ray
Mantoux test
Gastric wash
GeneXpert test- The New Era
As with any disease, diagnosis is the key to treatment. There are a lot of obstacles in proper diagnosis of TB in HIV children.
Some of the methods we use are:
Recognizing symptoms: It is the physicians responsibility to be able to recognize symptoms of TB when a child is brought in and then order the routine test from there.
Contact history: This is based on voluntary information from parent. This becomes a challenge since most mother who bring in their children are unaware of other family member who are in charge of taking care of their children have contracted TB.
Culture method: This is done by ordering specific test
Chest X-ray: This shows infected lung

7. Symptoms Coughing >2 weeks Chest pain Weakness or fatigue
Weight Loss> 10%
Fever/Chill
Night Sweat
Some common symptoms for TB is shown on the slide. READ FROM SLIDE
However some of these information, such as – how long has the child been coughing for, has to be provided by the parent. We often find that parent who bring in their children are not able to provide these records.

8. Recognizing Symptoms Probable TB +ive tuberculin skin test
>Suggestive chest radiography. ie Lymphadenopathy, pericardial effusion etc.
>CT Scan ,ie Chest, Abdomen, brain
Suggestive histological appearance on biopsy material- FNA
Favourable response to TB-specific therapy
When a child is suspected of TB, specific test are carried out to determine if indeed the child probably has TB.
Probable tuberculosis
Suspected TB with any of the following
• positive indurations on tuberculin skin test,
• suggestive appearance on chest radiograph
• suggestive histological appearance on biopsy material
• favourable response to TB-specific therapy.

9. Smear –ive TB is too confusing How do we understand it?
Cough for more then 14 days.
Chest pain more then 14 days
Weight loss >10%
Failure to gain weight despite ART
Minimal or No Sputum production
Irrespective of proper Antibiotics cough does not disappear, one should think of TB in 1st then consider thinking malignancy(mostly in adult).
HIV patients must not be loosing weight after initiating ART, if such happened physician should exclude TB.

10. Cont’d Lymphadenopathy i.e. X-ray Severe anemia, Hb < 7gm
Signs of extra pulmonary TB
Milliary pattern on chest x-ray
If severe shortness of breath, we will consider PCP first.
In extra pulmonary TB patients might not have cough, but other symptoms will persists.

11. Baby born to Mother with TB
If Baby has no TB signs or symptoms
Start with Isoniazide 10mg/kg/day for 6 months.
Once IPT completed, BCG can be given if asymptomatic and HIV- uninfected.
TST can be done on child after 3 months of IPT.
If TST negative and mother smear negative , stop INH & give BCG.
Mother is positive and TB treatment/or not on RX during delivery

12. Baby Born to a Mother with TB
If haveing TB signs/Symptoms in Infant
Submission of gastric aspirates and blood for TB culture DST
CXR
Abdominal sonar ( as the liver is often the primary site in congenital TB).
IF TB Diagnosed.
Start Regimen 3 of TB treatment.
Start Fast track for ART if baby is HIV- infected.
A portion of placenta in sterile saline have to send for TB culture, another portion in formalin have to send for histology.

13. Statistics of Smear Negative TB
33-50% HIV +ve PTB patient were smear –ve
Kenya (2003)
64% HIV +ve patient with proven TB were AFB smear –ive
South Africa (2008)
26% of patient entering ART had active PTB
87% were AFB smear –ve even with fluorescent microscopy test.
This statistics are mostly of sub- sharan Africa's.

14. Cont’d
Smear –ive have high mortality rate even with proper TB treatment
HIV +ive patient have less TB organism in sputum even with low CD4 count.
Limited lab tech and high sample load- smear +ve missed
Ref- TB in ERA of HIV by Jon Fielder
This TB in HIV Era was published in Kanya.

15. Challenges Failure to recognizing symptoms Resource shortage
Lack in education
Adverse drug interaction
Our biggest challenge is failing to recognize symptoms. This may be partly due to ignorance on part of the childs parent/caregiver to provide information. This is often compounded by the Childs inability to describe the symptoms.
The next challenge we face in the public health care sector is chronic human resource shortage and limited resources. This makes delivery of health service particularly difficult.
What I see in my practice is a lack of education. Parent/Guardian need to be educated. I see children coming in wrapped all over in amulets and talisman given by traditional healers or elders. I also see reluctance of parent/guardian to take these off children during medical treatment. I totally respect the culture. These are age-old traditions and may have benefits. But being trained as a medical profession, I am more inclined toward proven scientific evidence.
These children already have a weakened immune system. Sometime they react negatively to the multiple drug prescribed to them. These also have to be carefully monitored and managed.

16. WHO Global TB Report
The pie chart give you an idea the extent to which TB is underdiagnosed in 2008.
This poses both clinical challenges and technological need.

17. Interpreting Mantoux test
Non-reactive
Reactive
Had BCG
< 15mm
> 15mm
No BCG
< 10mm
> 10mm
HIV +ve
< 4mm
> 4mm
After tuberculin test within hrs if induration is there – interrupted as above.
This Mantoux test interpolation is from our Guide book. Compiled by Dr Beker, Dr Von Royon, and approved by Dr Von Lobensten.

18. Tuberculosis creates cavities visible in x-rays like this one in the patients right upper lobe.

19. This X ray shows right lower zone consolidation.

20. Extra Pulmonary TB in Children
Peripheral Lymphadenitis
Bones and Joints ,spinal TB
Plural Effusion.
TB Pericarditis
Abdominal TB
TB Meningitis
In the late stage HIV TB can be anywhere in the body.
Other than lungs, TB can be anywhere in the body, possible site are as above.

21. Objective Of TB Treatment
To cure the patient
To prevent death
To prevent relapse
To prevent development of drug resistance
To reduce transmission
The main objective of TB treatment are
To cure the patient of TB- This is done by rapidly eliminating most of the bacilli
To prevent death from active TB
To prevent relapse of TB- this is done by eliminating any dormant bacilli
To prevent development of drug resistance-this is done by using a combination of drugs
To reduce transmission of TB, by using musk and isolation in some case if possible.

22. Treatment WHO Guideline
should be
treated with a four-drug regimen (RHZE) for 2 months followed by a two-drug
regimen (RH) for 4 months total 6 months.
TBM with HIV needs 9 to 12 months regime.
at the following dosages

23. Children in High HIV Setting
isoniazid (H)
10 mg/kg (range 10–15mg/kg)
maximum dose 300 mg/day
rifampicin (R)
15 mg/kg (range 10–20 mg/kg)
maximum dose 600 mg/day
pyrazinamide (Z)
35 mg/kg (30–40 mg/kg)
ethambutol (E)
20 mg/kg (15-25 mg/kg)
This recommendation is given by WHO
Children living in settings where the prevalence of the HIV is high or where
resistance to isoniazid is high, or both, with suspected or confirmed pulmonary
tuberculosis or peripheral lymphadenitis; or children with extensive pulmonary
disease living in settings of low HIV prevalence or low isoniazid resistance, should be
treated with a four-drug regimen (HRZE) for 2 months followed by a two-drug
regimen (HR) for 4 months at the following dosages:
isoniazid (H) – 10 mg/kg (range 10–15 mg/kg); maximum dose 300 mg/day
rifampicin (R) – 15 mg/kg (range 10–20 mg/kg); maximum dose 600 mg/day
pyrazinamide (Z) – 35 mg/kg (30–40 mg/kg)
ethambutol (E) – 20 mg/kg (15-25 mg/kg)

24. Monitoring Symptom assessment Adherence and reviewing treatment
Adverse events- LFT’s, haematology
rashes, IRIS
Regular follow-ups
Non-response to drugs- MDR TB
These children must be monitored constantly. The problem we face here in South Africa, is that parents do not bring back the children for follow up. This poses a problem in the long run.

25. How should we manage a child who deteriorates in TB treatment.
Is the drug dose is correct?
Is the child taking the drug as prescribed? (good adherence, including DOT)
Is the child HIV infected?
Is the child severely malnourished?
Is there is a reason to suspect MDR TB?
Has child develops IRIS?
Is there another reason for child illness other than TB, ie Malignancy?
We have to Consider all of the above, and short out one by one. then only possibly we will get the answer.

26. NEW Developments
In the last section of my talk I’ll be focusing on a new development in early detection of TB. The microscopy sputum test have long been used. Though a very very reliable method, it is time consuming. This new technology is the GeneXpert test.

27. GeneXpert Test GeneXpert MTB/RIF test
PCR based analysis.
Endorsed by WHO in Dec 2010 for adults
Research being conducted in SA since 2008.
The Xpert MTB/RIF detects DNA sequence specific for Mycobacterium tuberculosis and rifampicin resistance by polymerase chain reaction. WHO endorsed it for use in TB endemic countries.
Research is being conducted in South Africa to see the effectiveness of the process. Though long term data is still not available, so far it seems quite promising.

28. Advantages Provides results in ~90 min Minimal biohazard
Operation requires little technical training
The advantage of this method is that unlike other method, it is rapid and gives results within as little as 90min with minimal biohazard.
Also the operation is quite straight forward and requires little technical assistance.

29. “If a minister can do it, it can’t be that hard," Health Minister Aaron Moatsoaled.
This is a picture of the honourable Minister operating the Genexpert.

30. Can GeneXpert be used for children?
Yes according to WHO ?
if able to produce sputum or if an induced sputum is obtained
Gastric Aspiration fluid, Biopsy serous fluid.
Mark U of Cape Town
More effective Vs smear microscopy
Works better in HIV +ve children
Yes according to WHO. This is a relatively new procedure effective since dec 2010 and we do not have enough data yet to support. But based on generalization of data from adult WHO has given approval. Research is still being conducted here in South Africa.
Mark Nichol at the University of Cape Town is conducting work to evaluate GeneXpert in children. He published a study Accuracy of Xpert MTB/RIF test for the diagnosis of pulmonary tuberculosis in children admitted to hospital in Cape Town, South Africa: a descriptive study,” focusing on children of median age of 19 months.
It was clear from his study that GeneXpert is a more effective diagnostic tool than smear microscopy. Also GeneXpert seem to work better in HIV +ve children than HIV –ve children, let us hope for the best.

31. Disadvantages Cost- Requires uninterrupted electric supply
$16 for cartridge/ per test.
Requires uninterrupted electric supply
Requires calibration
However this new technology does come with certain disadvantages.
The cost is quite high.
The commonly used GX4 model which allows test per 8 hour shift costs about US $17000 with cartridge cost of $16 per cartridge. There are however more sophisticated models which can perform up to 1000 test at the same time, but the purchase cost is quite high.
The machine requires a stable uninterrupted electric supply. This can sometimes get difficult in developing countries.
The machine requires calibration from time to time which is to be performed by a skilled technician using specialize tools.

32. Summary- TB in Era of HIV
TB is surging in much of Africa because of the HIV epidemic.
The TB rates are usually higher than what is reported in the public health system.
TB is the number one cause of death in HIV-infected patients in Africa.
TB has usually spread through out the body by the time of death.
The patterns of TB diseases are changing.
TB is a multisystem disease.
TB can present as acute illness like pneumonia .
Tb must be treated before starting ARV treatment, it again depends on case to case.
ART can decrease new cases of TB and death rate.
Only half of the TB patients are diagnosed when the patients are alive.

33. Recommendations Good Record-keeping Group nutrition counselling
HIV/TB awareness education
Fundraising
All most all of the PHC , District and Provincial Hospital do keep TB and HIV record, still it is in paper based. Time has come to change from paper to computer?
In group nutrition- the patients, parents or caregiver and dietician should sit together monthly for better outcome.
HIV/TB awareness education should be given by all means, radio,tv,newspaper, school, college, churceses,mosqueses etc.

34. OUR CHILDREN ARE OUR FUTURE
Concluding Remarks
HIV/AIDS is the major threat to TB control
TB/HIV rates directly proportional to each other.
Overcoming challenges
OUR CHILDREN ARE OUR FUTURE
HIV/AIDs is a major threat to TB control. The two seems to be directly proportional. TB rate will plateau once HIV infection does.
I’ve talked about some of the challenges we face in diagnosis of patients and the resource constraints that we have. We need to overcome these . More funding is required for research from both the government and private sector in the battle against this deadly disease.
Our children are our future. Let us all work together to make this world better and disease free for all of us.

35. THANK YOU